1.Association Between Diabetes and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis of Observational Studies
Ana Paula PAGANO ; Bruna Ramos da SILVA ; Flávio Teixeira VIEIRA ; Luiz Fernando Meira FILHO ; Sarah A. PURCELL ; John D. LEWIS ; Michelle L. MACKENZIE ; Paula J. ROBSON ; Jennifer E. VENA ; Flávia Moraes SILVA ; Carla M. PRADO
The World Journal of Men's Health 2025;43(2):304-320
Purpose:
Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk.
Materials and Methods:
A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.
Results:
Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61–0.83, I2=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79–1.13, I2=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77–1.18, I2=98%) at diagnosis. According to GRADE, the evidence certainty was very low.
Conclusions
Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.
2.International Severe Asthma Registry (ISAR): 2017–2024 Status and Progress Update
Désirée LARENAS-LINNEMANN ; Chin Kook RHEE ; Alan ALTRAJA ; John BUSBY ; Trung N. TRAN ; Eileen WANG ; Todor A. POPOV ; Patrick D. MITCHELL ; Paul E. PFEFFER ; Roy Alton PLEASANTS ; Rohit KATIAL ; Mariko Siyue KOH ; Arnaud BOURDIN ; Florence SCHLEICH ; Jorge MÁSPERO ; Mark HEW ; Matthew J. PETERS ; David J. JACKSON ; George C. CHRISTOFF ; Luis PEREZ-DE-LLANO ; Ivan CHERREZ- OJEDA ; João A. FONSECA ; Richard W. COSTELLO ; Carlos A. TORRES-DUQUE ; Piotr KUNA ; Andrew N. MENZIES-GOW ; Neda STJEPANOVIC ; Peter G. GIBSON ; Paulo Márcio PITREZ ; Celine BERGERON ; Celeste M. PORSBJERG ; Camille TAILLÉ ; Christian TAUBE ; Nikolaos G. PAPADOPOULOS ; Andriana I. PAPAIOANNOU ; Sundeep SALVI ; Giorgio Walter CANONICA ; Enrico HEFFLER ; Takashi IWANAGA ; Mona S. AL-AHMAD ; Sverre LEHMANN ; Riyad AL-LEHEBI ; Borja G. COSIO ; Diahn-Warng PERNG ; Bassam MAHBOUB ; Liam G. HEANEY ; Pujan H. PATEL ; Njira LUGOGO ; Michael E. WECHSLER ; Lakmini BULATHSINHALA ; Victoria CARTER ; Kirsty FLETTON ; David L. NEIL ; Ghislaine SCELO ; David B. PRICE
Tuberculosis and Respiratory Diseases 2025;88(2):193-215
The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.
3.Association Between Diabetes and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis of Observational Studies
Ana Paula PAGANO ; Bruna Ramos da SILVA ; Flávio Teixeira VIEIRA ; Luiz Fernando Meira FILHO ; Sarah A. PURCELL ; John D. LEWIS ; Michelle L. MACKENZIE ; Paula J. ROBSON ; Jennifer E. VENA ; Flávia Moraes SILVA ; Carla M. PRADO
The World Journal of Men's Health 2025;43(2):304-320
Purpose:
Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk.
Materials and Methods:
A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.
Results:
Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61–0.83, I2=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79–1.13, I2=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77–1.18, I2=98%) at diagnosis. According to GRADE, the evidence certainty was very low.
Conclusions
Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.
4.International Severe Asthma Registry (ISAR): 2017–2024 Status and Progress Update
Désirée LARENAS-LINNEMANN ; Chin Kook RHEE ; Alan ALTRAJA ; John BUSBY ; Trung N. TRAN ; Eileen WANG ; Todor A. POPOV ; Patrick D. MITCHELL ; Paul E. PFEFFER ; Roy Alton PLEASANTS ; Rohit KATIAL ; Mariko Siyue KOH ; Arnaud BOURDIN ; Florence SCHLEICH ; Jorge MÁSPERO ; Mark HEW ; Matthew J. PETERS ; David J. JACKSON ; George C. CHRISTOFF ; Luis PEREZ-DE-LLANO ; Ivan CHERREZ- OJEDA ; João A. FONSECA ; Richard W. COSTELLO ; Carlos A. TORRES-DUQUE ; Piotr KUNA ; Andrew N. MENZIES-GOW ; Neda STJEPANOVIC ; Peter G. GIBSON ; Paulo Márcio PITREZ ; Celine BERGERON ; Celeste M. PORSBJERG ; Camille TAILLÉ ; Christian TAUBE ; Nikolaos G. PAPADOPOULOS ; Andriana I. PAPAIOANNOU ; Sundeep SALVI ; Giorgio Walter CANONICA ; Enrico HEFFLER ; Takashi IWANAGA ; Mona S. AL-AHMAD ; Sverre LEHMANN ; Riyad AL-LEHEBI ; Borja G. COSIO ; Diahn-Warng PERNG ; Bassam MAHBOUB ; Liam G. HEANEY ; Pujan H. PATEL ; Njira LUGOGO ; Michael E. WECHSLER ; Lakmini BULATHSINHALA ; Victoria CARTER ; Kirsty FLETTON ; David L. NEIL ; Ghislaine SCELO ; David B. PRICE
Tuberculosis and Respiratory Diseases 2025;88(2):193-215
The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.
5.Trends in knowledge, attitude and perceptions about HIV among Filipinos during and after the COVID-19 pandemic: Responses from a digital survey.
Glyzelle Anne A. Lagason ; Judith Anne Rose Y. Ganaden ; Martin Xavier D. Peñ ; aflor ; Ericson P. Acapulco ; Kristine T. Donarye ; John Alexander L. Fellizar ; Ma. Tarcela S. Gler
Acta Medica Philippina 2025;59(Early Access 2025):1-6
BACKGROUND
The Philippines has been significantly affected by the HIV epidemic in the Asia-Pacific region, with a notable increase in new cases over the past decade. Despite efforts to promote HIV testing, access to treatment, and awareness campaigns, progress has been slow, particularly among youths. Tangere, a market research application, conducted surveys during and after the COVID-19 pandemic to assess HIV knowledge among Filipinos.
OBJECTIVESThis study aimed to evaluate changes in HIV awareness among young Filipinos during and after the COVID-19 pandemic using data collected via Tangere’s surveys. Specifically, it sought to analyze demographic characteristics, sources of HIV information, and knowledge regarding HIV transmission, prevention, and stigma.
METHODSTangere collaborated with the investigators to develop a questionnaire assessing HIV knowledge among young Filipinos. Surveys were conducted during and after the COVID-19 pandemic, targeting subscribers aged 18-35 years, primarily from the National Capital Region and Luzon area. Data analysis involved calculating frequencies and percentages to summarize demographic characteristics and HIV knowledge. An Independent-Samples Proportions procedure was used to compare HIV knowledge during and after the pandemic.
RESULTSThe survey revealed that while respondents generally possessed reasonable knowledge about HIV, there were notable changes in the awareness during and after the pandemic. Social media and television were identified as primary sources of HIV information. Knowledge regarding HIV transmission and prevention increased postpandemic, particularly concerning preventive measures such as pre-exposure prophylaxis (PREP) and motherto-child transmission (MTCT). However, persistent misconceptions and stigma surrounding HIV remained, indicating the need for continued education and advocacy efforts.
CONCLUSIONThe study underscores the importance of utilizing social media platforms for HIV awareness campaigns, especially among youths who are disproportionately affected by the epidemic. Despite improvements in knowledge, the Philippines has yet to achieve global HIV prevention goals. Continued efforts to enhance awareness, particularly regarding recent advancements in HIV prevention and treatment, are essential for curbing the epidemic and improving public health outcomes nationwide.
Human ; Knowledge ; Attitude ; Hiv ; Covid-19 ; Pandemics
6.Lived experiences of well-being of the University Athletic Association of the Philippines Season 84 student-athletes in bubble training during the COVID-19 pandemic: A qualitative phenomenological study
Ken Erbvin R. Sosa ; Charles Nicolei M. Nermal ; Karlos Lorenzo A. Rea ; Gabrielle Atasha Tanhueco ; Isaac Miguel M. Andico ; Janelle Audre C. Chiu ; Timothy D. Lao ; Ma. Julia Isabelle G. peñ ; aloza ; John Mari R. Quilang ; Zeuch Ryonin B. Silva
Acta Medica Philippina 2025;59(Early Access 2025):1-18
BACKGROUND AND OBJECTIVE
The COVID-19 pandemic has disrupted the sports industry, resulting in the postponement of events worldwide. This posed a significant burden in the mental and emotional well-being of athletes due to uncertainties and diminished training levels. As an adaptation, bubble camps emerged as a new approach to resuming training and tournaments under stringent regulations of the COVID-19 protocols. In the national context, the University Athletic Association of the Philippines (UAAP) has adapted the bubble set-up by implementing antigen testing, RTPCR, and other health protocols as a prerequisite to bubble training. However, uncertainties in the future of sports continue to present as a psychological toll to the well-being of student-athletes despite the sense of normalcy instilled by bubble training. Existing literature on bubble training is grounded heavily on the quantitative assessments of an athlete's well-being in a bubble set-up and its effectiveness in mitigating COVID-19 transmission, thereby lacking insights that may be obtained from qualitative data. This study explored the experiences of UAAP Season 84 studentathletes in a bubble set-up by examining personal and contextual factors that impacted their well-being.
METHODSThe study employed a qualitative descriptive phenomenological approach based on Seligman's WellBeing Theory. A purposeful sampling technique was used to recruit UAAP student-athletes through online dissemination of Google Forms for recruitment. Only three student-athletes from UAAP fit the eligibility criteria. Data were collected through on-site and online interviews using a semi-structured interview guide to reveal a narrative of the student-athletes' bubble training experiences, common themes, and patterns. The NVivo software program was used for data analysis, utilizing a deductive thematic approach.
RESULTSThe lived experiences of three UAAP studentathletes were classified into six major themes: (1) Availability and Accessibility of Services; (2) Restrictions; (3) Mental Health; (4) Fostering Relationships; (5) Support Systems; and (6) Individual Growth. Accounts of both positive and negative training perceptions and outcomes regarding the bubble set-up were noted from all student-athletes. The set-up provided studentathletes with easy access to training facilities and services, eventual development of mental fortitude and perseverance, improved interpersonal relationships, and opportunities for individual growth. However, the restrictions, isolation, internal and external pressures, and routinary nature of the set-up contributed to the elevated levels of stress and anxiety, eventually leading to fatigue and burnout.
CONCLUSIONThe study elucidates on the multi-faceted experiences of UAAP student-athletes in bubble training, underpinning the essence of the adequacy of training services and facilities, enhanced support systems, and prompt policy development that caters to improving the holistic well-being of student-athletes amidst adverse changes in the trajectory of sports.
Human ; Qualitative Research ; Universities ; College Athletes ; Athletes
7.Association Between Diabetes and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis of Observational Studies
Ana Paula PAGANO ; Bruna Ramos da SILVA ; Flávio Teixeira VIEIRA ; Luiz Fernando Meira FILHO ; Sarah A. PURCELL ; John D. LEWIS ; Michelle L. MACKENZIE ; Paula J. ROBSON ; Jennifer E. VENA ; Flávia Moraes SILVA ; Carla M. PRADO
The World Journal of Men's Health 2025;43(2):304-320
Purpose:
Metabolic diseases such as diabetes mellitus may play a role in the development and progression of prostate cancer (PC); however, this association remains to be explored in the context of specific PC stages. The objective of this study was to systematically review the evidence for an association between diabetes and overall, early, or advanced PC risk.
Materials and Methods:
A systematic review with meta-analysis was performed (MEDLINE, EMBASE, and CINAHL) from inception until September 2023. Cohort and case-control studies that assessed PC risk in adult males (≥18 years) associated with type 2 diabetes mellitus or diabetes (if there was no distinction between diabetes type) were included. The Newcastle-Ottawa Scale (NOS) was used to assess study bias; those with NOS<7 were excluded. Evidence certainty was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.
Results:
Thirty-four studies (n=26 cohorts and n=8 case-controls) were included. Of these, 32 assessed diabetes and all PC stages combined, 12 included early PC stages, and 15 included advanced PC stages. Our meta-analysis showed diabetes had a protective effect against early PC development (n=11, risk ratio [RR]=0.71; 95% confidence interval [CI]=0.61–0.83, I2=84%) but no association was found for combined (n=21, RR=0.95; 95% CI=0.79–1.13, I2=99%) or advanced PC stages (n=15, RR=0.96; 95% CI=0.77–1.18, I2=98%) at diagnosis. According to GRADE, the evidence certainty was very low.
Conclusions
Diabetes may be protective against early PC stages, yet evidence linking diabetes to risk across all stages, and advanced PC specifically, is less conclusive. High heterogeneity may partially explain discrepancy in findings and was mostly associated with study design, method used for PC diagnosis, and risk measures. Our results may aid risk stratification of males with diabetes and inform new approaches for PC screening in this group, especially considering the reduced sensitivity of prostate-specific antigen values for those with diabetes.
8.International Severe Asthma Registry (ISAR): 2017–2024 Status and Progress Update
Désirée LARENAS-LINNEMANN ; Chin Kook RHEE ; Alan ALTRAJA ; John BUSBY ; Trung N. TRAN ; Eileen WANG ; Todor A. POPOV ; Patrick D. MITCHELL ; Paul E. PFEFFER ; Roy Alton PLEASANTS ; Rohit KATIAL ; Mariko Siyue KOH ; Arnaud BOURDIN ; Florence SCHLEICH ; Jorge MÁSPERO ; Mark HEW ; Matthew J. PETERS ; David J. JACKSON ; George C. CHRISTOFF ; Luis PEREZ-DE-LLANO ; Ivan CHERREZ- OJEDA ; João A. FONSECA ; Richard W. COSTELLO ; Carlos A. TORRES-DUQUE ; Piotr KUNA ; Andrew N. MENZIES-GOW ; Neda STJEPANOVIC ; Peter G. GIBSON ; Paulo Márcio PITREZ ; Celine BERGERON ; Celeste M. PORSBJERG ; Camille TAILLÉ ; Christian TAUBE ; Nikolaos G. PAPADOPOULOS ; Andriana I. PAPAIOANNOU ; Sundeep SALVI ; Giorgio Walter CANONICA ; Enrico HEFFLER ; Takashi IWANAGA ; Mona S. AL-AHMAD ; Sverre LEHMANN ; Riyad AL-LEHEBI ; Borja G. COSIO ; Diahn-Warng PERNG ; Bassam MAHBOUB ; Liam G. HEANEY ; Pujan H. PATEL ; Njira LUGOGO ; Michael E. WECHSLER ; Lakmini BULATHSINHALA ; Victoria CARTER ; Kirsty FLETTON ; David L. NEIL ; Ghislaine SCELO ; David B. PRICE
Tuberculosis and Respiratory Diseases 2025;88(2):193-215
The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.
9.Investigation of selective glucocorticoid receptor modulation in high-grade serous ovarian cancer PDX models
Manisha TAYA ; Xiaonan HOU ; Jennifer T. VENERIS ; Nina KAZI ; Melissa C. LARSON ; Matthew J. MAURER ; Ethan P. HEINZEN ; Hao CHEN ; Ricardo LASTRA ; Ann L. OBERG ; S. John WEROHA ; Gini F. FLEMING ; Suzanne D. CONZEN
Journal of Gynecologic Oncology 2025;36(1):e4-
Objective:
In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX).
Methods:
Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography.
Results:
One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response.
Conclusion
The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.
10.Investigation of selective glucocorticoid receptor modulation in high-grade serous ovarian cancer PDX models
Manisha TAYA ; Xiaonan HOU ; Jennifer T. VENERIS ; Nina KAZI ; Melissa C. LARSON ; Matthew J. MAURER ; Ethan P. HEINZEN ; Hao CHEN ; Ricardo LASTRA ; Ann L. OBERG ; S. John WEROHA ; Gini F. FLEMING ; Suzanne D. CONZEN
Journal of Gynecologic Oncology 2025;36(1):e4-
Objective:
In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX).
Methods:
Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography.
Results:
One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response.
Conclusion
The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.


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